Dual Antiplatelet Therapy in Patients With Clopidogrel Resistance Following Off-Pump Coronary Artery Bypass

Dual Antiplatelet Therapy in Patients With Clopidogrel Resistance Following Off-Pump Coronary Artery Bypass: Prospective, Randomized Controlled Trial

Ticagrelor, a direct-acting oral P2Y12-receptor antagonist, provides greater and more consistent platelet inhibition than clopidogrel. This study aimed to compare outcomes of ticagrelor plus aspirin versus clopidogrel plus aspirin 1 year after off-pump coronary artery bypass grafting (OPCAB) in patients with clopidogrel resistance.

Study Overview

• Status: Not yet recruiting
• Conditions: Multi Vessel Coronary Artery Disease
• Intervention / Treatment: Drug: Ticagrelor; Drug: Clopidogrel

Detailed Description

Between November 2014 and November 2020, 1739 patients underwent OPCAB. Aspirin (100mg daily) and clopidogrel (75mg daily) were administered beginning at aday 1 after surgery. On the 7th postoperative day, the clopidogrel resistance was evaluated by point-of-care assay. Among them, the patients had clopidogrel resistance were enrolled in this study. Investigators divide them into two groups [A: ticagrelor, B; clopidogrel]. Primary endpoint was all-cause of mortality 1 year after OPCAB. Secondary endpoint included major adverse cardiovascular events (MACE: cardiac death, myocardial infarction, or stroke). Multivariate Cox regression was used to evaluate predictors of end points.

• Study Type: Interventional
• Enrollment (Anticipated): 204
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Young-Nam Youn; Phone Number: 82-10-9930-4522; Email: ysgs@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients aged 19 years or older
2. undergoing elective OPCAB surgery with multi-vessel coronary artery disease.

Exclusion Criteria:

1) patient had aspirin resistance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clopidogrel	Drug: Clopidogrel; platelet aggregation inhibitor; Other Names: plavix
Experimental: Ticagrelor	Drug: Ticagrelor; direct-acting oral P2Y12-receptor antagonist; Other Names: brilinta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early graft patency	graft occlusion rate diagnosed by CT exam, at follow-up angiography, grafts were evaluated by use of the usual definition of patency and were assessed for FitzGibbon patency with the A, B, and O classification system in which FitzGibbon A is an excellent/unimpaired graft, Bis an impaired graft with a stenosis >50% reducing the caliber of the graft to <50% of the target artery diameter, and O is a completely occluded graft.	1 year after OPCAB

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
degree of resistance	Platelet reactivity was assayed using the VeriofyNowP2Y12 assay (Accumetrics Inc, San Diego, CA) which is a cartridge-based assay that specifically measures the direct effects of clopidogrel on the platelet P2Y12 receptor. The results are expressed as P2Y12 reaction units (PRUs) for clopidogrel. The cut-off PRU value was 188 PRU and the details were described previous study.	7 day after surgery
Number of patients with resistance with clopidogrel as assessed by VeriofyNowP2Y12 assay	The cut-off PRU value was 188 PRU	7 day after surgery
Mediastinal Bleeding	total drainage counts (ml) from median tubes	up to 4 weeks
Total hospital day from admission to discharge		up to 4 weeks
rate of postoperative stroke of myocardial infarction		Participants will be followed during 1 years from operation
rate of postoperative morbidity/ mortality		Participants will be followed during 5 years from operation

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Varma PK, Ahmed H, Krishna N, Jose R, Gopal K, Mathew OP, Jayant A. Bleeding complications after dual antiplatelet therapy with ticagrelor versus dual antiplatelet therapy with clopidogrel-a propensity-matched comparative study of two antiplatelet regimes in off-pump coronary artery bypass grafting. Indian J Thorac Cardiovasc Surg. 2021 Jan;37(1):27-37. doi: 10.1007/s12055-020-01052-6. Epub 2020 Oct 7.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: December 20, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Actual): December 22, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Coronary artery bypass surgery; Antiplatelets
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: 2021-2374-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No